1. Field of the Invention
The present invention relates to the field of blood component transfusion, specifically in a new method of treatment to decrease the need for transfusion such as red blood cell and platelet transfusion in human and animal patients. Transfusion of blood components can mitigate the morbidity in patients suffering from, for example, insufficient concentrations of red blood cells, white blood cells and platelets, in vivo, due to various causes. A new method of treatment to decrease the need for transfusion with natural blood components or to replace them is especially vital to the recovery of some patients who are particularly susceptible to the effects of radiation, burn or chemotherapy treatment.
2. Description of the Prior Art
Exposure to massive doses of ionizing radiation, such as after a dirty-bomb or atomic-bomb explosion, or a nuclear-reactor or medical radiation accident, can lead to major morbidity and/or mortality. If the victim survives the direct effect of the bomb blast, he still may suffer from damages to the nervous, digestive, pulmonary, hematopoietic and other vital systems. Published articles have revealed that transfusion of blood components, e.g. red blood cells and platelets can decrease the morbidity and mortality among irradiated patients. In these situations, blood components can be the main method of treatment without the concomitant use of other treatments, or the blood components can be used as an adjunct, to be used in conjunction with other treatments, such as those to be mentioned below. However, the infrastructures for the procurement, maintenance and distribution of blood components are not reliable during war times or when a national crisis has occurred.
One group of patients is particularly susceptible to the ill effects of agents that can lead to suboptimal concentrations of red blood cells, white blood cells and platelets in vivo, including agents such as irradiation, burn and chemotherapy. These are patients who are on anti-platelet treatment or anti-coagulation treatment for a variety of reasons. They will have excessive internal bleeding and increased morbidity and mortality compared to patients who are not on such anti-platelet or anti-coagulation treatments.
Various methods have been employed to treat radiation sickness, all with limited success. For example: (1) Neumune, an androstenediol, had been used by the US Armed Forces Radiobiology Research Institute under joint development with Hollis-Eden Pharmaceuticals; (2) A Chinese herbal medicine called Cordyceps sinensis had been used to try to protect the bone marrow and digestion systems of mice after whole body irradiation; (3) Bisphosphonate compounds had also been tried; (4) U.S. Pat. No. 6,916,795 disclosed an “energy-protective composition” comprising adenosine phosphates; (5) Garnett and Remo disclosed at the International Symposium on Application of Enzymes in Chemical and Biological Defense, Plenary Session Abstract, May 2001 that “DNA Reductase” had some “Opportunist Clinical Activity Against Radiation Sickness”; and (6) U.S. Pat. No. 6,262,019 disclosed a composition called MAXGXL which contains glytathione. All of the above are soluble enzymes, steroids or small molecules.
Of particular interest is the discussion listed under: http://nextbigfuture.com/2009/07/radiation-sickness-cures-and-anti.html
It discussed:
(1) the effect of a small-molecule inhibitor to the p53-mediated apoptosis. A single shot of this drug, called CBLB502, at less than 1% of the maximum dose resulted in an 87% survival rate of mice exposed to an otherwise lethal dose of 13 Gray of radiation. By comparison, even at the maximum dose of the second-best chemical, called amifostine, only 54% of similarly irradiated mice survived.
(2) The work done at the Boston University School of Medicine on new compounds called the “EUK-400 series” which may be taken orally.
(3) DARPA funded work done at the Rice University called “Nanovector Trojan Horses, NTH.” These carbon nanotube-based drugs may scavenge free radicals and mitigate the effects of ionizing radiation.
All of the above treatments employ mechanisms very different from the present invention. While some of the above mentioned treatments may result in improved survival of irradiated patients, it is not clear if the survivors will have other long-term medical problems caused by the irradiation or by the treatment. Therefore there is need for a new treatment that will improve survival, yet with less or no long-term medical problems among the survivors, caused either by the radiation or by the side-effects of the treatment.
In this application the term “improved survival” or “to improve survival” can mean: (1) a prolong survival time, e.g. if 100% of the irradiated subjects will die before day-30 without treatment, a treatment will be considered effective in prolonging life if it takes longer than 30 days (e.g. a year) before 100% of a similarly irradiated group dies (possibly from other problems); or (2) an increase in the survival rate at a fixed time (e.g. 30-day survival rate, or 90-day survival rate) after irradiation. Also the irradiation dose can be maximally lethal, leading to 100% of the irradiated subjects dying if untreated; or minimally lethal, having only, e.g. 5% of the irradiated subjects dying—both will be called “a lethal dose of irradiation.”
While the above-mentioned prior-art treatment methods fulfill their respective, particular objectives, requirements and are aimed at improving survival of irradiated subjects, it is not clear that these treatments can result in fewer units of blood components being needed to support the patient during treatment. Therefore a new method of treatment is needed which can decrease the need for transfusion, whether in the frequency or in the amount of transfusion of blood components, whether the above-mentioned prior-art treatment methods were concomitantly used for the patient or not.
In addition, it would be most preferable that the new method of treatment will be able to improve survival all by itself without the use of any blood components or the use of any prior-art treatment for irradiated patients.
Moreover, it would be highly preferable that the new method of treatment will be able to decrease the morbidity of irradiated subjects all by itself without the use of any blood components or the use of any prior-art treatment for irradiated patients. Less morbid patients can assist themselves and use up less of the vital medical resources. Also, a patient that is not actively bleeding is more likely to receive help in a time of crisis than another one that is oozing blood.
The new method of treatment that can decrease the use of blood components will also be useful in cancer patients whose blood producing capacity is diminished, or patients receiving chemotherapy or radiation therapy, or any other medical, surgical, trauma patient in need of blood component therapy, including and not limited to red blood cell transfusion, platelet transfusion, coagulation factor infusion, recombinant factor therapy, interleukin and cytokine treatment.
The term “blood component” in this invention can mean any protein and non-protein component extracted from blood, or a product manufactured in vitro as a molecule or as a recombinant product based on the gene or genes known to code for the naturally-made blood component. It can include cellular and non-cellular components of blood.
Examples in this application include patients exposed to radiation. It is to be understood that the beneficial effects of the present invention is not limited to irradiated patients, but will include people exposed to thermal burns (external and internal), radiation burns, viral infections that cause bleeding, or people suffering from cancer, chemotherapy, and all kinds of procedures requiring transfusion of different kinds of blood cells to increase cell counts, such as patients who are septic or undergoing disseminated intravascular coagulation (DIC), thrombotic or hemorrhagic episodes, idiopathic (or immunological) thrombocytopenic purpura (ITP) or surgical patients.
Part of the information disclosed in this application was filed with the USPTO as a provisional application, No. 61/281,466 (“Submicron Particles for the Treatment of Radiation Damage in Patients”) and as a non-provisional application, filed Nov. 16, 2010, USPTO Ser. No. 12/927,543, revealing an early date of invention. The entire disclosures of these prior applications are incorporated herein by reference.
Therefore, a need exists for new and improved submicron particles to decrease transfusion that can be used for treatment to decrease the need for transfusion such as red blood cell and platelet transfusion in human and animal patients. In this regard, the present invention substantially fulfills this need. In this respect, the submicron particles to decrease transfusion according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in doing so provides an apparatus primarily developed for the purpose of treating to decrease the need for transfusion such as red blood cell and platelet transfusion in human and animal patients.